It is proposed to continue a research program designed to provide information about DNA base damage and its effects. The quantities and types of damage to thymine and adenine bases produced by ionizing radiation in vivo will be determined in bacterial strains selected for their known radiation sensitivities and for their genetically characterized ability to repair radiation damage. Specific products of base damage, such as thymine glycols, will be measured as a function of radiation dose, and time after irradiation during the period in which radiation damage is thought to be repaired. Since it has been found that damaged and undamaged base residues (bases, nucleosides, oligonucleotides) are released from DNA immediately after irradiation, these residues will be identified and quantitated as a function of bacterial strain and postirradiation incubation time. The effect of O2 and several cis-platinum antitumor drugs on the quantities and types of DNA base damage as well as on base residue release will be determined. Selected types of DNA (such as platinized DNA) will be subjected to pulse radiolysis studies at the NIH-funded Center for Fast Kinetics Research at U. of Texas, Austin. These studies will help to elucidate possible changes in reactivity of DNA transient radicals when the DNA contains bound drugs.